Originally used in 1906 by Von Pirquet, the term "allergy" means a change in the reactions of the host when in contact with an "agent" called antigen or allergen. Nevertheless, the immunological mechanisms responsible for the signs and symptoms observed in allergic subjects are the normal body defense mechanisms common to all individuals. The difference is that, in allergic subjects, the body's immune response to antigens exceeds the aims of protection and becomes harmful for the subject himself. There is a very marked difference in the sensitivity of the immune response between the allergic subject and the non-allergic subject. For this reason, it is now generally preferred to use the terms hypersensitivity, rather than allergy, to describe the particular reactivity of the allergic subject in response to antigens. The allergic subject actually reacts to very small quantities of substances present in the environment, such as house dust and pollen, which, in the majority of people, do not provoke any particular reaction as they are minimally antigenic. These substances are not dangerous in themselves, but, in allergic subjects, they induce a series of immunological responses resulting in an episode of allergy, harmful for the host and for the tissues in which it develops.
Coombs and Gell have described four types of hypersensitivity reactions (Type I, II, III and IV) but in practice, these types do not necessarily occur separately from each other. The first three types are antibody (immunoglobulin) mediated, and the fourth is mediated primarily by specialized cells. In the recent years, "allergy" has become synonymous with Type I hypersensitivity in which the reactions are dependent on the specific triggering of immunoglobulin E (IgE) -sensitized mast cells by antigen resulting in the degranulation of mast cells and the release of pharmaceutically mediators of inflammation, such as histamine, leukotrienes and prostaglandins that cause vasodilatation, increased capillary permeability, smooth muscle contraction, and eosinophilia. Type I hypersensitivity may be followed by Type III hypersensitivity reaction when antigen meets antibody (primarily IgG and IgA) at body surfaces, for example in the lungs, the nose and eye, leading to the formation of antigen-antibody immune complexes which trigger a variety of inflammatory processes. They can interact with the complement system leading to the generation of anaphylatoxins C3a and C5a which have potential inflammatory effects and cause the release of vasoactive amines from the mast cells and basophils, thus increasing vascular permeability and attracting polymorphs. Activation of the complement system can also lead to the release of cytolytic components that are able to damage tissues. The mechanisms of hypersensitivity reaction involving mast cell degranulation and complement activation are described in detail in the following book; Immunology, I. Roitt (Sections 7, 19, 21 in particular).
The allergen present in the environment and capable of inducing allergic reactions in predisposed subjects are very diverse. The most usual ones are pollens, house dust, moulds, feather, animal furs and danders. Pollens are a very frequent cause of seasonal conjunctival and nasal allergic reactions ("hay fever") and bronchial allergy (asthma). House dust is principally responsible for perennial allergies which can affect the lungs (asthma), the nose (rhinitis) and the eye (conjunctivitis). The allergenic substances present in house dust are produced by microscopic mites belonging to the arthropod class. Moulds can also be responsible for allergic reactions since they are widely spread in nature and their spores are dispersed in great quantities by the wind. Animal furs and danders are among the most potent allergens. Domestic animals such as cats and dogs are frequent causes of respiratory allergies. The feathers contained in bedding are frequently accused of being responsible for allergic symptoms, however, it appears that in the great majority of cases, the allergen responsible is not the actual feather, but the Dermatophagoides mites which multiply in the feather used for beddings.
This list of the principal allergens is obviously not exhaustive. Any substance capable of triggering an immune response and participating in an immunological reaction is potentially allergenic. Countless numbers of substances are able to enter the body, induce a sensitization process and induce allergic reaction.
The reasons why certain subjects react to substances in the environment to which the majority of subjects remain insensitive remain largely unexplained. However, it is known that among the causative factors, genetic predisposition for allergy, environmental conditions (exposure to allergens) and local tissue factors play an important role.
The initial step in the sensitization process is the penetration of the allergen into the mucosa. Because of their exposure to the environment, the conjunctival, nasal, bronchial and mucosae are more frequently the site of sensitization processes than other mucous membranes.
The surface of the mucosa is endowed with mechanical defense mechanisms (mucus and mucociliary transport in the respiratory tract, lacrimal film in the eye) and immunological defense mechanisms (secretory immunoglobulin A) which normally constitute effective barriers to prevent the penetration of antigenic substances.
It is possible that allergic subjects present a fundamental or transient anomaly in these natural defenses, responsible for the penetration and persistence of allergens in the mucosa. In addition to this constitutional or acquired defect in the system of elimination of allergens, the immunological defense system in allergic subjects also has a particular predisposition for recognizing -as a result of a particularly accurate "memory"--very small quantities of an allergenic substance with which it has previously been in contact.
The anti-allergic drugs of the prior art may be classified in three categories:
coricosteroids which act on the cellular inflammation factors, PA0 mast-cell degranulation inhibitors, PA0 antihistamines. PA0 in the eye, in the treatment of allergic conjunctivitis, PA0 in the nose, in the treatment of allergic rhinitis, PA0 in the bronchi, in the treatment of asthma of allergic origin, PA0 on the skin, in the treatment of dermatitis of allergic origin.